The molecular mechanisms that underlie spleen development and congenital asplenia, a condition linked to increased risk of overwhelming infections, remain largely unknown. The transcription factor TLX1 controls cell fate specification and organ expansion during spleen development, and Tlx1 deletion causes asplenia in mice. Deregulation of TLX1 expression has recently been proposed in the pathogenesis of congenital asplenia in patients carrying mutations of the gene-encoding transcription factor SF-1. Herein, we have shown that TLX1-dependent regulation of retinoic acid (RA) metabolism is critical for spleen organogenesis. In a murine model, loss of Tlx1 during formation of the splenic anlage increased RA signaling by regulating several genes involved in RA metabolism. Uncontrolled RA activity resulted in premature differentiation of mesenchymal cells and reduced vasculogenesis of the splenic primordium. Pharmacological inhibition of RA signaling in Tlx1-deficient animals partially rescued the spleen defect. Finally, spleen growth was impaired in mice lacking either cytochrome P450 26B1 (Cyp26b1), which results in excess RA, or retinol dehydrogenase 10 (Rdh10), which results in RA deficiency. Together, these findings establish TLX1 as a critical regulator of RA metabolism and provide mechanistic insights into the molecular determinants of human congenital asplenia.

SUMMARY: TargetFinder is a new software tool to search a database of annotated sequences for transcription factor binding sites located in context with other important transcription regulatory signals and regions, like the TATA element, the promoter, and so on, thereby greatly reducing the background usually associated with this kind of search. AVAILABILITY: The TargetFinder Web service is available at http://hercules.tigem.it/TargetFinder.html CONTACT: giovanni.lavorgna@hsr.it

We recently identified the long non-coding RNA (ncRNA) TRPM2-AS as a key regulator of survival in prostate cancer [1]. This essential role, coupled to the TRPM2-AS low-expression levels in healthy tissues, makes this ncRNA a suitable therapeutic target for further clinical studies. To get insights into the survival mechanism controlled by this molecule, we ablated its expression in prostate cancer cells and performed a genome-wide analysis of the transcripts differentially regulated in dying cells. Here, we describe in detail the experimental system, methods and quality control for the generation of the microarray data associated with our recent publication [1]. The data are related to [1]. Data have been deposited to the Gene Expression Omnibus (GEO) database repository with the dataset identifier GSE40687.